Zenitz et al. U.S. Pat. No. 3,198,798 and Van Dyke U.S. Pat. No. 3,579,524 and British Pat. No. 942,866 disclose 3-oxoisoindole compounds with piperazinylalkylene or substituted piperazinylalkylene moiety on the isoindole N-substiuent. Zenitz et al. discloses antihypertensive utility as well as utility for treating disturbances of the gastrointestinal tract. Van Dyke discloses antihypertensive utility. The British patent discloses that its compounds have anaesthetic, spasmolytic and pectoral properties.
It can be of advantage in the treatment of some disorders to utilize a single drug having both antihypertensive activity and diuretic (especially natriuretic) activity. Usually, the opposite is the case. For example, prazosin, a very active antihypertensive agent has antidiuretic activity.
Thus, there is active research for novel antihypertensive and/or diuretic agents.
For instance, a compound reported in the literature as having diuretic and hypertensive activity is chlorexolone which has the structural formula ##STR3## In this regard, see Cornish, et al., J. Pharm. Pharmacol., 18, 65-80 (1966) and Himori, et al., Jpn. J. Pharmacol., 1978, 28(6), 811-818 (Chem. Abs. 90: 97589t) and Suzuki, et al., Nippon Yakurigaku Zasshi, 1972, 63(3), 276-289 (Chem. Abs. 81: 58265d). Cornish, et al. disclose the preparation of phthalimides and 1-oxoisoindolines related to the diuretic chlorexolone. Himori, et al. studied the antihypertensive effect of a combination of chlorexolone and the .beta.-adrenergic blocking agent alprenolol in conscious renal hypertensive dogs and found a significant decrease in blood pressure after the second day of treatment. Suzuki, et al. reported that the hypotensive diuretics, hydroflumethiazide, triamterene, chlorexolone, etc. have favorable effects in the spontaneously hypertensive rat.
Thus, while particular compounds with 6-chloro-5-sulfamoyl isoindolinyl moiety have been known or reputed to have diuretic and antihypertensive activity and while particular isoindolinyl-alkyl-piperazines are disclosed as having antihypertensive activity, 6-chloro-5-sulfamoyl isoindolinyl-alkyl-piperazines have heretofore been unknown.
As used herein the term diuretic means increased total urine flow and/or increased sodium elimination.